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. 2021 Feb 16:2021:4034509.
doi: 10.1155/2021/4034509. eCollection 2021.

Associations among Cognitive Functions, Plasma DNA, and Diffusion Tensor Image along the Perivascular Space (DTI-ALPS) in Patients with Parkinson's Disease

Hsiu-Ling Chen  1 , Pei-Chin Chen  1 , Cheng-Hsien Lu  2 , Nai-Wen Tsai  2 , Chiun-Chieh Yu  1 , Kun-Hsien Chou  3   4 , Yun-Ru Lai  2 , Toshiaki Taoka  5 , Wei-Che Lin  1
Affiliations

Associations among Cognitive Functions, Plasma DNA, and Diffusion Tensor Image along the Perivascular Space (DTI-ALPS) in Patients with Parkinson's Disease

Hsiu-Ling Chen et al. Oxid Med Cell Longev. .

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disease associated with accumulation of misfolding proteins and increased neuroinflammation, which may further impair the glymphatic system. The purpose of this study was to utilize diffusion tensor image analysis along the perivascular space (DTI-ALPS) to evaluate glymphatic system activity and its relationship with systemic oxidative stress status in PD patients.

Methods: Magnetic resonance imaging and neuropsychological tests were conducted on 25 PD patients with normal cognition (PDN), 25 PD patients with mild cognitive impairment (PD-MCI), 38 PD patients with dementia (PDD), and 47 normal controls (NC). Oxidative stress status was assessed by plasma DNA level. Differences in ALPS-index among the subgroups were assessed and further correlated with cognitive functions and plasma DNA levels.

Results: The PD-MCI and PDD groups showed significantly lower ALPS-index compared to normal controls. The ALPS-index was inversely correlated with plasma nuclear DNA, mitochondrial DNA levels, and cognitive scores.

Conclusions: Lower diffusivity along the perivascular space, represented by lower ALPS-index, indicates impairment of the glymphatic system in PD patients. The correlation between elevated plasma nuclear DNA levels and lower ALPS-index supports the notion that PD patients may exhibit increased oxidative stress associated with glymphatic system microstructural alterations.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Illustration of the brain waste clearance between the perivascular space and glymphatic system. The glymphatic system is a waste drainage system in which cerebrospinal fluid (CSF) in the para-arterial space exchanges with interstitial fluid (ISF) with the aid of aquaporin-4 (AQP4) water channels on the astroglial endfeet and is drained into the perivascular space, from which it eventually reaches the lymphatic nodes. The system is driven by para-arterial ISF bulk influx (red arrow), glymphatic ISF bulk influx (blue arrow), and para-venous CSF-ISF efflux (green arrow). In disease status, such as neurodegeneration disorder, neuroinflammation in interaction with systemic oxidative stress can alter the function of BBB and astrocytes and waste clearance efficiency in the glymphatic system.
Figure 2
Figure 2
(a) DTI color map shows the direction of the projection fibers (blue; z-axis), association fibers (green; y-axis), and the subcortical fibers (red; x-axis). Three ROIs are placed to measure diffusivities of the three fibers. (b) Schematic diagram presents the relationship between the direction of the perivascular space (gray cylinders), the fibers, and the formula of the ALPS-index. Note that the direction of the perivascular space is perpendicular to both projection and association fibers.
Figure 3
Figure 3
Quantitative analysis of the ALPS-index in the PDN, PD-MCI, PDD patient groups (a), and in the early PD and late PD patient groups (b) in comparison with the healthy control group.
Figure 4
Figure 4
Correlation among the ALPS-index, plasma DNA, and cognitive function in the NC and PD group (a) and in the PD subgroups (b).
See this image and copyright information in PMC

References

    1. Braak H., Rub U., Jansen Steur E. N. H., del Tredici K., de Vos R. A. I. Cognitive status correlates with neuropathologic stage in Parkinson disease. Neurology. 2005;64(8):1404–1410. doi: 10.1212/01.WNL.0000158422.41380.82. - DOI - PubMed
    1. Irwin D. J., White M. T., Toledo J. B., et al. Neuropathologic substrates of Parkinson disease dementia. Annals of Neurology. 2012;72(4):587–598. doi: 10.1002/ana.23659. - DOI - PMC - PubMed
    1. Ransohoff R. M. How neuroinflammation contributes to neurodegeneration. Science. 2016;353(6301):777–783. doi: 10.1126/science.aag2590. - DOI - PubMed
    1. Iliff J. J., Wang M., Liao Y., et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid. Science Translational Medicine. 2012;4(147, article 147ra111) doi: 10.1126/scitranslmed.3003748. - DOI - PMC - PubMed
    1. Chiang P. L., Chen H. L., Lu C. H., et al. Interaction of systemic oxidative stress and mesial temporal network degeneration in Parkinson’s disease with and without cognitive impairment. Journal of Neuroinflammation. 2018;15(1):p. 281. doi: 10.1186/s12974-018-1317-z. - DOI - PMC - PubMed